This project will explore the anatomical and physiological correlates of neuronal interactions in a well defined system involving Neuropeptide Y (NPY) neurons which innervate the paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei. Neuropeptide Y, a 36 amino acid peptide, is one member of a newly recognized peptide family also containing peptide YY and pancreatic polypeptide. Within the gastrointestinal tract and peripheral nervous system, these peptides have been demonstrated to be biologically active and to subserve a number of functional roles. In the central nervous system, however, nothing is known regarding the role of the numerous and widely distributed NPY neurons. This project will begin to investigate the anatomical and physiological roles of NPY neurons innervating two morphologically and physiologically well defined nuclei, the PVN and SON. These nuclei are known to be important both in neuroendocrine and central autonomic functioning, and have been implicated in limbic and cortical functioning as well. Using a variety of techniques, including peptide immunohistochemistry, fluorescent retrograde and lectin anterograde neuronal tract tracing, double-labeling methods and electron microscopic immunocytochemistry, we will determine the anatomical interactions of NPY axons with chemically defined neurons of the PVN and SON. We will assess the synaptic relationship of NPY terminals within each of the subnuclei of the PVN and SON known to contain CRF, vasopressin (VP) and oxytocin (OX) neurons. The origin of these NPY terminals will also be determined. The role of NPY coexisting in catecholamine neurons innervating the PVN and SON will be investigated, and we will attempt to determine whether NPY and norepinephrine coexist within the same synaptic vesicles. We will compare the development of the NPY innervation with the appearance of CRF, VP and OX neurons in the PVN and SON to determine if the target neuron peptide is required to establish appropriate innervation. Finally, we will investigate the physiological effect of NPY on VP release in vitro by using the organ-cultured rat hypothalamo-neurohypophyseal system.